Natural Progression Model of Cognition and Physical Functioning among People with Mild Cognitive Impairment and Alzheimer's Disease

Ron L. H. Handels*, Weili Xu, Debora Rizzuto, Barbara Caracciolo, Rui Wang, Bengt Winblad, Frans R. J. Verhey, Johan L. Severens, Laura Fratiglioni, Manuela A. Joore, Anders Wimo

*Corresponding author for this work

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Background: Empirical models of the natural history of Alzheimer's disease (AD) may help to evaluate new interventions for AD. Objective: We aimed to estimate AD-free survival time in people with mild cognitive impairment (MCI) and decline of cognitive and physical function in AD cases. Methods: Within the Kungsholmen project, 153 incident MCI and 323 incident AD cases (international criteria) were identified during 9 years of follow-up in a cognitively healthy cohort of elderly people aged >= 75 at baseline (n = 1,082). Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and daily life function was evaluated with the Katz index of activities of daily living (ADL) at each follow-up examination. Data were analyzed using parametric survival analysis and mixed effect models. Results: Median AD-free survival time of 153 participants with incident MCI was 3.5 years. Among 323 incident AD cases, the cognitive decline was 1.84 MMSE points per year, which was significantly associated with age. Physical functioning declined by 0.38 ADL points per year and was significantly associated with age, education, and MMSE, but not with gender. Conclusion: Elderly people with MCI may develop AD in approximately 3.5 years. Both cognitive and physical function may decline gradually after AD onset. The empirical models can be used to evaluate long-term disease progression of new interventions for AD.
Original languageEnglish
Pages (from-to)357-365
JournalJournal of Alzheimer's Disease
Issue number2
Publication statusPublished - 2013


  • Alzheimer's disease
  • dementia
  • disease progression
  • economic model
  • mild cognitive impairment

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